The mechanism of action of DNA-reactive antitumor drugs such as DNA strand scission agents like neocarzinostatin, macromomycin and bleomycin and intercalation agents like adriamycin and daunorubicin will be studied by examination of their effects on chromatin and nucleosome structure. Chromatin and nucleosomes from drug-treated cells will be mapped for DNA damage sites to determine what regions of the DNA are susceptible to attack by the drugs' nuclease activity. A similar study to determine DNA damage sites will be done using isolated chromatin and nucleosomes. The effect of intercalation drugs on chromatin will be analyzed by spectral techniques and also studies will be done to determine the interaction of these drugs with DNA strand scission drugs. Mechanism of drug action studies will also examine the effects of DNA strand scission drugs using tumor virus SV40 as a model system. A comparison will be made between the ability of these drugs to cut cell-free purified SV40 DNA in vitro and SV40 DNA isolated from drug-treated purified virus. Also the ability of these drugs to alter viral infectivity and propagation will be explored and correlated with the drug's ability to cut viral DNA.